World Immunization Week 2018

Vaccines are widely recognized as one of the world’s most successful and cost-effective health interventions. In fact, vaccines designed to prevent deadly diseases such as polio, smallpox, and measles have saved millions of lives.

Life-saving Interventions: The Most Successful Vaccines in Recent History

Polio Vaccine

During the first half of the 20^th century, summertime wasn’t a synonym for carefree fun in the sun, but instead was known as “polio season.” Infants and young children were particularly susceptible to contracting the polio virus – a disease that affects the central nervous system and can cause permanent paralysis. At its peak in the early 1950s, 25,000 to 50,000 new cases of polio occurred each year.

But two researchers, Jonas Salk and Albert Sabin, were on separate missions to develop a vaccine to combat this devastating disease. Both researchers were dedicated to finding a vaccine to prevent polio, but they took very different paths. Salk focused his work on a “killed virus,” meaning he injected a dead version of the polio virus via needle into a patient’s blood stream, while Sabin developed an oral “live” polio vaccine that was ingested rather than injected.

While Salk completed his vaccine ahead of Sabin, the oral polio vaccine is the most widely used today, as it is the most effective and simplest to administer. Importantly, neither scientist ever patented their vaccine formulas, making them accessible and affordable in resource-limited settings. During an interview with Edward R. Murrow, Salk famously was asked why he never patented his version of the vaccine, to which he replied, “Because it is for the people; could you patent the sun?”

Thanks to access to polio vaccines, the disease has been eliminated in all but three countries: Afghanistan, Pakistan, and Nigeria. However, as long as the disease remains endemic in these countries, the entire world is at risk for another polio outbreak.

Smallpox

Smallpox is the only disease in human history that has been completely wiped off the planet. A vaccine for smallpox was first developed in 1796, also making the smallpox vaccine the first effective vaccine to be used to prevent disease.

The vaccine’s unprecedented and so far un-replicated success can be attributed to many factors, but most importantly to the worldwide cooperation between country governments and the World Health Organization (WHO) beginning in the 1960s. Public health workers were able to administer the vaccine on a mass scale across populations, even administering vaccines in dangerous war zones to reach enough of the population to eventually eradicate the disease.

The last known case of Smallpox occurred in Somalia and 1977, and it was declared officially eradicated by the WHO in 1980.

Measles, Mumps, and Rubella

Once seen as inevitable childhood diseases, measles, mumps, and rubella (MMR) cases have been drastically reduced around the world thanks to the MMR vaccine. It was first introduced in the United States in 1971 and has since been used widely around the world to prevent these three diseases in children and adults. Now administered during childhood in two doses, the combination vaccine was developed to induce immunity less painfully and sooner and more efficiently than three injections given on different dates.

In 1978, the U.S. Centers for Disease Control and Prevention (CDC) set a goal to eliminate measles from the United States by 1982. Although this goal was not met, widespread use of measles vaccine drastically reduced the disease rates. By 1981, the number of reported measles cases was 80% less compared with the previous year.

The MMR vaccine has also been used worldwide, averting more than 1.5 million deaths. However, recent outbreaks in the United States and Europe highlight the need for continued education efforts around the vaccine’s effectiveness and its importance in preventing diseases.

Rotavirus

Rotavirus is the most common cause of diarrheal disease (DD) and is the second-leading killer disease of children under five around the world. This crisis is especially critical where safe water, sanitation, and access to urgent medical care are limited. Children in these regions can quickly succumb to dehydration and malnutrition from DD. Even when it doesn’t kill, repeated bouts of DD can lead to irreversible physical and cognitive stunting, a burden that contributes to keeping families locked in a cycle of poverty.

However, nearly every child in the world, no matter they live, is at risk for rotavirus. In the United States, rotavirus caused about 3 million cases of DD prior to the vaccine’s introduction in 2006. Today, thanks to the vaccine – co-invented by Paul Offit, MD, a professor of Pediatrics at Penn and director of the Vaccine Education Center at Children's Hospital of Philadelphia – hospitalizations and deaths from rotavirus have been drastically reduced, and the vaccine has been found to be between 80 and 100 percent effective against the disease.

Next on the Vaccine Horizon

HIV/AIDS

When the AIDS epidemic first took hold in the United States more than 30 years ago, doctors were at a loss for how to treat or prevent this mysterious and deadly illness that seemed to primarily affect gay men. Today, HIV/AIDS is a worldwide global health crisis that has claimed the lives of more than 38 million men, women, and children. In recent years, much progress has been made on the HIV treatment and prevention fronts.

Antiretroviral therapy (ART) is helping people with HIV live longer, healthier lives while also reducing the risk of passing the virus to others. Yet a vaccine to prevent HIV remains elusive. However, researchers at Penn and around the world are hopeful that a breakthrough is just around the corner.

In 2016, Pablo Tebas, MD, director of the Therapeutic Clinical Trials Unit at Penn, and his team began working with researchers across the country to find an effective immunotherapy approach to treating HIV that could eventually lead to a functional cure. The study, which was published in the New England Journal of Medicine, examined  chronically HIV-infected participants and found that injections of one broadly neutralizing HIV antibody (bNAb), known as VRC01, were safe, generated high levels of the antibody, and modestly delayed the time of HIV viral rebound.

By demonstrating that HIV-specific antibodies could be successfully administered as long-acting agents to suppress or even kill HIV-infected cells, this method is a first step toward the ultimate goal of durable suppression of HIV in the absence of ART.

Zika

The Zika outbreaks of 2015-2016 continue to reap consequences today. Thousands of children born during that time period now suffer from microcephaly and other neurological diseases from contracting the virus in utero from their mothers. The growing concern over Zika prompted researchers at Penn to explore a Zika vaccine candidate.

In 2016, Pablo Tebas, MD, and his team partnered with the Wistar Institute and Inovio/GeneOne Pharmaceuticals to develop a DNA-based Zika vaccine, which was recently found to demonstrate both safety and the ability to elicit an immune response against Zika in humans. Unlike other common vaccines in which a virus protein is injected, this vaccine injects DNA into the skin, where a large amount of immune cells exist in the body. The DNA is then uptaken by cells that will produce a particular Zika virus protein. The hope is that antibodies against that Zika protein will develop to prevent infection.

“We do not inject the virus itself, so there is no risk of participants becoming infected with Zika from the vaccine,” said Tebas, a professor of Infectious Diseases at the Perelman School of Medicine and a principal investigator on the trial.

Drew Weissman, MD, PhD, a professor of Infectious Diseases and his team are also working a Zika vaccine candidate that uses RNA strands to protect against the virus. Found to be effective with single dose in pre-clinical trials, Weissman and his team hope to begin human trials this year.

Vaccines for diseases such as Zika and HIV/AIDS are some of the many in development to cure the next generation of deadline global diseases. Which one will be the first to see the same success as efforts to end polio and smallpox remains to be seen, but one thing is certain: thanks to the dedication of vaccine researchers, progress will continue until we see the end of these and other devastating diseases.